Summary: Molecular genetic principles will be used to produce murine analogs of inherited human diseases for which spontaneous mutants are not available. Development of a transgenic mouse model of Gaucher's disease is a high priority aspect of this project. Murine genomic and cDNA clones were obtained, characterized, and mapped to mouse chromosome 3 and introduced into murine embryonic stem cells grown in cell culture. Methods have been devised using the PCR and Southern blot techniques to identify which few clones of the 108 progenitor cells that were electroporated are the cells carrying an inactivated glucocerebrosidase gene.